Taxonomic distribution of proteins containing SCY domains

The tree below includes only several representative species and genera. The complete taxonomic breakdown of all proteins containing SCY domains can be accessed here. Click the counts or percentage values to display the corresponding proteins.

Human chemokines: an update.

Baggiolini M, Dewald B, Moser B
Annu Rev Immunol. 1997; 15: 675-705

Interleukin 8, the first chemokine to be characterized, was discovered nearly ten years ago. Today, more than 30 human chemokines are known. They are often upregulated in inflammation and act mainly on leukocytes inducing migration and release responses. The present review deals largely with the new developments of the last three years. Several structural studies have shown that most chemokines form dimers. The dimers, however, dissociate upon dilution, and the monomers constitute the biologically active form. Chemokine activities are mediated by seven-transmembrane-domain, G protein coupled receptors, five of which were discovered in the past three years. The primary receptor-binding domain of all chemokines is near the NH2 terminus, and antagonists can be obtained by truncation or substitutions in this region. Major progress has been made in the understanding of chemokine actions on T lymphocytes that respond to several CC chemokines but also to IP10 and Mig, two CXC chemokines that selectively attract T cells via a novel receptor. Effects of chemokines on angiogenesis and tumor growth have been reported, but the data are still contradictory and the mechanisms unknown. Of considerable interest is the recent discovery that some chemokines function as HIV-suppressive factors by interacting with chemokine receptors which, together with CD4, were recognized as the binding sites for HIV-1.

The immunobiology of interferon-gamma inducible protein 10 kD (IP-10): a novel, pleiotropic member of the C-X-C chemokine superfamily.

Neville LF, Mathiak G, Bagasra O
Cytokine Growth Factor Rev. 1997; 8: 207-19

Interferon-gamma inducible protein 10 kD (IP-10) is a highly inducible, primary response gene that belongs to the C-X-C chemokine superfamily. Despite the original cloning of IP-10 in 1985, its biological functions are still unclear although accumulating reports indicate that it is a pleiotropic molecule capable of eliciting potent biological effects, including stimulation of monocytes, natural killer and T-cell migration, regulation of T-cell and bone marrow progenitor maturation, modulation of adhesion molecule expression as well as inhibition of angiogenesis. More interest is now likely to be focused on IP-10 due to the recent cloning of an IP-10 receptor. This paper aims to highlight our current knowledge of IP-10 and its homologues as well as defining its likely involvement in regulating fibroproliferation following inflammatory lung injury.

Interleukin-8 and related chemotactic cytokines--CXC and CC chemokines.

Baggiolini M, Dewald B, Moser B
Adv Immunol. 1994; 55: 97-179

Interleukin-8, a chemotactic and inflammatory cytokine.

Baggiolini M, Clark-Lewis I
FEBS Lett. 1992; 307: 97-101

Interleukin-8 (IL-8) belongs to a family of small, structurally related cytokines similar to platelet factor 4. It is produced by phagocytes and mesenchymal cells exposed to inflammatory stimuli (e.g., interleukin-1 or tumor necrosis factor) and activates neutrophils inducing chemotaxis, exocytosis and the respiratory burst. In vivo, IL-8 elicits a massive neutrophil accumulation at the site of injection. Five neutrophil-activating cytokines similar to IL-8 in structure and function have been identified recently. IL-8 and the related cytokines are produced in several tissues upon infection, inflammation, ischemia, trauma etc., and are thought to be the main cause of local neutrophil accumulation.

Three-dimensional structure of interleukin 8 in solution.

Clore GM, Appella E, Yamada M, Matsushima K, Gronenborn AM
Biochemistry. 1990; 29: 1689-96

The solution structure of the interleukin 8 (IL-8) dimer has been solved by nuclear magnetic resonance (NMR) spectroscopy and hybrid distance geometry-dynamical simulated annealing calculations. The structure determination is based on a total of 1880 experimental distance restraints (of which 82 are intersubunit) and 362 torsion angle restraints (comprising phi, psi, and chi 1 torsion angles). A total of 30 simulated annealing structures were calculated, and the atomic rms distribution about the mean coordinate positions (excluding residues 1-5 of each subunit) is 0.41 +/- 0.08 A for the backbone atoms and 0.90 +/- 0.08 A for all atoms. The three-dimensional solution structure of the IL-8 dimer reveals a structural motif in which two symmetry-related antiparallel alpha-helices, approximately 24 A long and separated by about 14 A, lie on top of a six-stranded antiparallel beta-sheet platform derived from two three-stranded Greek keys, one from each monomer unit. The general architecture is similar to that of the alpha 1/alpha 2 domains of the human class I histocompatibility antigen HLA-A2. It is suggested that the two alpha-helices form the binding site for the cellular receptor and that the specificity of IL-8, as well as that of a number of related proteins involved in cell-specific chemotaxis, mediation of cell growth, and the inflammatory response, is achieved by the distinct distribution of charged and polar residues at the surface of the helices.